The aims of this project are to study factors which regulate the perinatal pulmonary circulation. Of particular concern will be an evaluation of the role prostaglandins have in regulating blood flow through normal and abnormal perinatal lungs. Studies will be carried out on anesthetized newborn and exteriorized as well as unanesthetized in-utero fetal goats. Specifically, I wish to study: (1) metabolism of prostaglandins by maturing fetal and neonatal lungs; (2) interactions between prostaglandins and other vasoactive substances in controlling flow through the lungs; (3) effects of prostaglandin precursors on the perinatal pulmonary and systemic circulation; (4) effects of prostaglandin synthetase inhibitors on the changes in pulmonary vascular resistance at birth; (5) role of prostaglandins in the production of fetal lung liquid and; (6) the usefulness of dilator prostaglandins in reducing pulmonary vascular resistance in sheep models of persistent fetal pulmonary hypertension as well as in models of respiratory distress syndrome. The potential significance of this research lies in the fact that it is directly related to possible therapeutic measures which may be used in persistent pulmonary hypertension and respiratory distress. Also, the work should provide information on possible harmful side effects on the fetus and newborn of pharmacological agents such as indomethacin, aspirin and meclofenamate which are currently used clinically to prevent premature delivery as well as to close patent ductus arteriosus.